This invention relates to diagnosis, staging, and monitoring of treatment of malignancy disease.
Tests proposed for the detection of malignancy using blood plasma include measurements of carcinoembryonic antigen, beta-human chorionic gonadotropin, and alpha-fetoprotein in serum (P. H. Sugarbaker et al., 1982, Diagnosis and Staging, In: de Vita, et al., eds., Cancer: Principles and Practice of Oncology, J. B. Lippincott, Philadelphia, pages 248-54), and water-suppressed proton nuclear magnetic resonance (NMR) spectroscopy of plasma (E. T. Fossel, et al., 1986, New England J. Med., vol. 315(22), pages 1369-76).
K. Larsson et al., 1974, Experientia, vol. 30, pages 481-83, combined fluorescence and Raman spectra of plasma samples from healthy human subjects and from patients suffering from a variety of organic diseases including non-malignancy as well as malignanacy diseases. They noted that normal spectra have sharp Raman scattering bands at 1160 cm.sup.-1, 1520 cm.sup.-1, and 1010 cm.sup.-1, broad unresolved Raman bands at about 3400 cm.sup.-1, 3300 cm.sup.-1, and 2900 cm.sup.-1, and "[b]ackground fluorescence scattering characterized by moderate slope upwards in the range 1000 to 1600 cm.sup.-1, and a horizontal niveau or a slight slope upwards in the range 1600 to 2800 cm.sup.-1." They observed in samples from diseased individuals "strong changes in the background spectra due to ranges of the intrinsic fluorescence.
All patients with advanced carcinomas showed such a steep slope due to strong intrinsic fluorescence that the sharp Raman bands at 1160 and 1520 cm.sup.-1 did not even show up in the spectra."
A. J. Rein et al., 1976, Experientia, vol. 32, pages 1352-54, produced resonance Raman spectra of human blood plasma over the frequency range 900 cm.sup.-1 to 1600 cm.sup.-1 and showed that the bands at 1517 cm.sup.-1, 1157 cm.sup.-1, and 1005 cm.sup.-1 arise from carotenoids present in the plasma. Citing the work of K. Larsson et al., supra, they speculated that "[i]t may become possible, therefore, to both detect and investigate very specific disease states by examination of blood plasma using the rather unusual technique of resonance Raman spectroscopy."
G. Careri et al., 1970, Physics Letters, volume 32A(7), pages 495-496; J. P. Biscar et al., 1972, Chemical Physics Letters, volume 14(5), pages 569-7; and J. P. Biscar et al., 1973, Polymer Letters Edition, vol. 11, pages 725-29, studying the Raman behavior of purified proteins, demonstrated that some broad bands appearing in Raman spectrographs result from a "pseudo-Raman behavior", and not from intrinsic fluorescence, as generally assumed.
S. P. Verma et al., 1984, Biochem. Biophys. Res. Commun., vol. 122(2), pages 867-875; and S. P. Verma et al., 1985, Lipids, vol. 20(12), pages 890-896, suggested that differences in the resonance Raman spectra of human plasma lipoprotein carotenoids near the 1530 cm.sup.-1 band are caused by alterations in the lipid protein interactions of the carotenoid-carrying low-density lipoproteins (LDL). They assigned the 1160 cm.sup.-1 band to C--C bond stretching vibrations, and the 1530 cm.sup.-1 band to C.dbd.C bond stretching vibrations in the central part of the carotenoid chain.